Subjective Response to Alcohol as a Research Domain Criterion.

Individual differences in the subjective experience of the pharmacological effects of alcohol have long been implicated in the likelihood that one will drink heavily and develop alcoholism. The theme of this conceptual review and perspective article is to synthesize the literature on subjective responses to alcohol and to set an agenda for the next generation of research in the area. Specifically, we contend that in order for subjective response to alcohol to play a prominent role in alcoholism research, it is critical that it be studied as a multimodal phenotype.

First, we review the human research on subjective response to alcohol measured under controlled laboratory conditions and draw recommendations for the application of these findings to understanding alcoholism neurobiology in humans. Second, we highlight multimodal approaches, including studies of the genetic and neural substrates of individual differences in subjective response to alcohol. Third, we review treatment implications with a focus on subjective response to alcohol as an intervention target. Upon review of the research on subjective response to alcohol across levels of analyses, we provide recommendations for leveraging these phenotypes in a systematic and methodologically rigorous fashion that can address central questions about alcoholism etiology, disease progression, and personalized treatment.

The approach recommended herein is largely consistent with the Research Domain Criteria (RDoC) initiative across the National Institute of Mental Health. The defining feature of such domains is that they inform behavior yet be amenable to examination through multiple units of analysis, such as molecular, genetic, circuit-level, and behavioral measurements. To that end, we contend that subjective response to alcohol represents a behaviorally and biologically plausible phenotype upon which to build using the RDoC framework for understanding alcohol use disorder.